Curli, a unique class of fibers produced by Escherichia coli, are implicated in the formation of biofilms and sepsis in vivo and exhibit all the structural and biochemical properties of amyloid fibers involved in human pathologies such as Alzheimer's and Parkinson's diseases. The curli proteins CsgE and CsgF appear to act as molecular chaperones for the curli subunit proteins CsgA and CsgB as they traverse the periplasm and are predicted to have structural homology to the heat shock proteins DnaK and Hsp15. This proposal aims to 1) reveal the functions of CsgE and CsgF in curli biogenesis by determining their interaction partners and solving their three-dimensional structures and 2) access the overall role of curli in a well-established murine model of cystitis by monitoring curli expression during the normal course of infection with wild-type uropathogenic E. coli (UPEC) and by infecting with mutant strains that are curli-deficient or constitutively express curli proteins. The highly regulated curli assembly pathway provides an excellent opportunity to study factors involved in bacterial pathogenesis and those governing amyloid assembly generally, both of which may lead to new treatments for major human diseases.